The proposed research is directed at understanding principles of chromosome structure. Three specific questions will initially be asked: (i) What genetic decisions or information are required for formation of polytene chromosomes of Drosophila? (ii) What sequences at Drosophila chromosome region 11A are responsible for the properties of "intercalary heterochromatin" and meiotic recombination? (iii) Does the fragile-X mutation in human chromosomes, and a subsequent chromosome "imprint," lead to late-replicating DNA at Xq27? The health relatedness of this project is as follows: question (i) may lead to methods to induce polyteny in cultured human cells, which would provide useful material for human gene mapping; question (2) may provide insight in meiotic properties of Drosophila chromosomes that are applicable to the human fragile X chromosome; question (iii) is expected to provide direct information about the human fragile X mutation and putative chromosome imprinting event that are responsible for the most common cause of inherited mental retardation in humans. Methodologies involve cytogenetic, genetic, and molecular analysis of chromosomes and DNA. Recombinant DNA technology, DNA sequencing, P-element transformation of Drosophila, and genetic analysis will be used for this research.